Almost one million Americans die from cardiovascular disease each year and atherosclerosis is the underlying cause of the majority of adverse events including myocardial infarct (MI) and stroke. While anti-atherosclerotic drugs exist, current treatments are sub-optimal and new approaches to treat atherosclerosis are needed.
Atherosclerosis is a progressive vascular disease characterized by endothelial dysfunction, upregulation of cell adhesion molecules, accumulation of lipids, macrophages, smooth muscle cells (SMCs), and fibrous tissue in the arterial intima. The process of atherogenesis is still not completely understood, but it is generally accepted that inflammation plays an important role in all stages of atherosclerosis.
Chronic inflammatory reactions in the arterial wall promote the recruitment of macrophages, SMCs, progenitor stem cells, monocytes and T lymphocytes in the arterial intima. This accumulation is regulated by the expression of cell adhesion molecules, including the gap junction protein Connexin 43 (Cnx-43) and chemokines including Cxcl5 which direct the migration of leukocytes and stem cells to vascular injury sites. These chemokines are essential components of atherogenesis. Thrombosis or embolism in a large atherosclerotic artery such as the aorta or carotid may cause MI or ischemic stroke.
Current non-surgical treatment regimes for atherosclerosis include: 1) statins and niacin that reduce circulating lipid levels, cholesterol and triglycerides. 2) wafarin, aspirin, and clopidogrel, anticoagulants and anti-platelet agents that reduce thrombosis.